Efficacy and Safety of Low-dose Chemotherapy Plus Immuno-targeted Drugs in Newly Diagnosed Adult Ph- B-ALL

Summary

In the treatment of Ph-negative (Ph-) B-cell acute lymphoblastic leukemia (B-ALL) among adult patients, therapeutic outcomes remain suboptimal despite advances in chemotherapy and immunotherapy. A subset of adults with Ph- B-ALL have comorbidities or physiological limitations that preclude the safe administration of intensive regimens. In recent years, tumor immunotherapy has demonstrated promising safety and efficacy profiles in refractory or relapsed Ph- B-ALL across a wide spectrum of adult ages. These findings suggest that broader application of immunotherapy may represent a critical strategy to improve survival in this population. In this study, we propose a regimen that combines immuno-targeted agents with low-intensity chemotherapy for newly diagnosed adult patients with Ph- B-ALL. Our primary objective is to increase the rate of measurable residual disease (MRD)-negative complete remission (CR) following induction therapy, reduce the risk of relapse, and ultimately enhance overall survival.

Timeline

Start

2024-04-02

Primary completion

2026-12-01

Completion

2028-12-31

Publications

• Background Terwilliger T, Abdul-Hay M. Acute lymphoblastic leukemia: a comprehensive review and 2017 update. Blood Cancer J. 2017 Jun 30;7(6):e577. doi: 10.1038/bcj.2017.53.
• Background Pui CH, Yang JJ, Hunger SP, Pieters R, Schrappe M, Biondi A, Vora A, Baruchel A, Silverman LB, Schmiegelow K, Escherich G, Horibe K, Benoit YC, Izraeli S, Yeoh AE, Liang DC, Downing JR, Evans WE, Relling MV, Mullighan CG. Childhood Acute Lymphoblastic Leukemia: Progress Through Collaboration. J Clin Oncol. 2015 Sep 20;33(27):2938-48. doi: 10.1200/JCO.2014.59.1636. Epub 2015 Aug 24.
• Background Boissel N, Auclerc MF, Lheritier V, Perel Y, Thomas X, Leblanc T, Rousselot P, Cayuela JM, Gabert J, Fegueux N, Piguet C, Huguet-Rigal F, Berthou C, Boiron JM, Pautas C, Michel G, Fiere D, Leverger G, Dombret H, Baruchel A. Should adolescents with acute lymphoblastic leukemia be treated as old children or young adults? Comparison of the French FRALLE-93 and LALA-94 trials. J Clin Oncol. 2003 Mar 1;21(5):774-80. doi: 10.1200/JCO.2003.02.053. Epub 2003 Mar 1.
• Background O'Brien S, Thomas DA, Ravandi F, Faderl S, Pierce S, Kantarjian H. Results of the hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone regimen in elderly patients with acute lymphocytic leukemia. Cancer. 2008 Oct 15;113(8):2097-101. doi: 10.1002/cncr.23819.
• Background Geyer MB, Hsu M, Devlin SM, Tallman MS, Douer D, Park JH. Overall survival among older US adults with ALL remains low despite modest improvement since 1980: SEER analysis. Blood. 2017 Mar 30;129(13):1878-1881. doi: 10.1182/blood-2016-11-749507. Epub 2017 Jan 25. No abstract available.
• Background Maury S, Chevret S, Thomas X, Heim D, Leguay T, Huguet F, Chevallier P, Hunault M, Boissel N, Escoffre-Barbe M, Hess U, Vey N, Pignon JM, Braun T, Marolleau JP, Cahn JY, Chalandon Y, Lheritier V, Beldjord K, Bene MC, Ifrah N, Dombret H; for GRAALL. Rituximab in B-Lineage Adult Acute Lymphoblastic Leukemia. N Engl J Med. 2016 Sep 15;375(11):1044-53. doi: 10.1056/NEJMoa1605085.
• Background Kantarjian H, Stein A, Gokbuget N, Fielding AK, Schuh AC, Ribera JM, Wei A, Dombret H, Foa R, Bassan R, Arslan O, Sanz MA, Bergeron J, Demirkan F, Lech-Maranda E, Rambaldi A, Thomas X, Horst HA, Bruggemann M, Klapper W, Wood BL, Fleishman A, Nagorsen D, Holland C, Zimmerman Z, Topp MS. Blinatumomab versus Chemotherapy for Advanced Acute Lymphoblastic Leukemia. N Engl J Med. 2017 Mar 2;376(9):836-847. doi: 10.1056/NEJMoa1609783.
• Davis KL, Yao CC, Zimmerman JAO, Rau RE. Immunotherapy in B-Cell Acute Lymphoblastic Leukemia. J Natl Compr Canc Netw. 2025 Dec;23(12):e257067. doi: 10.6004/jnccn.2025.7067.

Drugs

Indications